Endothelial stunning and myocyte recovery after reperfusion of jeopardized muscle: A role of l-arginine blood cardioplegia

Byline: Asatoshi Mizuno, Rufus Baretti, Gerald D. Buckberg, Helen H. Young, Jakob Vinten-Johansen, Xin-Liang Ma, Louis J. Ignarro Abstract: Ischemia and reperfusion may damage myocytes and endothelium in jeopardized hearts. This study tested whether (1) endothelial dysfunction (reduced nitric oxide release) exists despite good contractile performance and (2) supplementation of blood cardioplegic solution with nitric oxide precursor l-arginine augments nitric oxide and restores endothelial function. Among 30 Yorkshire-Duroc pigs, 6 received standard glutamate/aspartate blood cardioplegic solution without global ischemia. Twenty-four underwent 20 minutes of 37[degrees] C global ischemia. Six received normal blood reperfusion. In 18, the aortic clamp remained in place 30 more minutes and all received 3 infusions of blood cardioplegic solution. In 6, the blood cardioplegic solution was unaltered; in 6, the blood cardioplegic solution contained l-arginine (a nitric oxide precursor) at 2 mmol/L; in 6, the blood cardioplegic solution contained the nitric oxide synthase inhibitor l-nitro arginine methyl ester (l-NAME) at 1 mmol/L. Complete contractile and endothelial recovery occurred without ischemia. In jeopardized hearts, complete systolic recovery followed infusion of blood cardioplegic solution and of blood cardioplegic solution plus l-arginine. Conversely, contractility recovered approximately 40% after infusion of normal blood and blood cardioplegic solution plus l-NAME. Postischemic nitric oxide production fell 50% in the groups that received blood cardioplegic solution and blood cardioplegic solution plus l-NAME but was increased in the group that received blood cardioplegic solution l-arginine. In vivo endothelium-dependent vasodilator responses to acetylcholine recovered 75% [+ or -] 5% of baseline in the blood cardioplegic solution plus l-arginine group, but less than 20% of baseline in other jeopardized hearts. Endothelium-independent smooth muscle responses to sodium nitroprusside were relatively unaltered. Myeloperoxidase activity (neutrophil accumulation) was similar in the blood cardioplegic solution (without ischemia) and blood cardioplegic solution plus l-arginine groups (0.01 [+ or -] 0.002 vs 0.013 [+ or -] 0.003 [mu]g/gm tissue). Myeloperoxidase activity was raised substantially to 0.033 [+ or -] 0.002 [mu]g/gm after exposure to normal blood and to 0.025 [+ or -] 0.003 [mu]g/gm after infusion of blood cardioplegic solution and was highest at 0.053 [+ or -] 0.01 [mu]g/gm with exposure to blood cardioplegic solution plus l-NAME in jeopardized hearts. The discrepancy between contractile recovery and endothelial dysfunction in jeopardized muscle can be reversed by adding l-arginine to blood cardioplegic solution. (J Thorac Cardiovasc Surg 1997;113:379-89) Article History: Received 22 May 1996; Revised 6 August 1996; Revised 30 August 1996; Accepted 9 September 1996 Article Note: (footnote) [star] Rufus Baretti was supported in full by the Deutsche Forschungsgemeinschaft (German Research Foundation)., [star][star] Read at the Seventy-sixth Annual Meeting of The American Association for Thoracic Surgery, San Diego, Calif., April 28-May 1, 1996., a Address for reprints: Gerald D. Buckberg, MD, UCLA School of Medicine, Division of Cardiothoracic Surgery, Room B2-375 CHS, 10833 Le Conte Ave., Los Angeles, CA 90095-1741., aa 0022-5223/97 $5.00 + 0 12/6/77854